Involvement of Nuclear Factor Kappa B in High-Fat Diet-Related Pancreatic Fibrosis in Rats
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background/Aims: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-κB)in high-fat diet-induced pancreatic fi brosis in rats. Methods:Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-κB-associated genes or protein expressions. Results: Infl ammation, fat deposition, pancreatic stellate cell activation and fi brosis were observed in the pancreases of the high-fat diet group. NF-κB subunit p65 (NF-κB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-κB/p65, ICAM-1and tumor necrosis factor α were all elevated signifi cantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed signifi cantly increased levels of ICAM-1and nuclear NF-κB/p65 in rats fed high-fat diets comparison with control rats. Conclusions: NF-κB is involved in high-fat diet-related pancreatic fi brosis.
Abstract
Background/Aims: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-κB)in high-fat diet-induced pancreatic fi brosis in rats. Methods:Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-κB-associated genes or protein expressions. Results: Infl ammation, fat deposition, pancreatic stellate cell activation and fi brosis were observed in the pancreases of the high-fat diet group. NF-κB subunit p65 (NF-κB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-κB/p65, ICAM-1and tumor necrosis factor α were all elevated signifi cantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed signifi cantly increased levels of ICAM-1and nuclear NF-κB/p65 in rats fed high-fat diets comparison with control rats. Conclusions: NF-κB is involved in high-fat diet-related pancreatic fi brosis.
참고문헌 (26)
- Popov D, "Saturated-fat diet induces moderate diabetes and severe glomerulosclerosis in hamsters", Diabetologia, 46, pp.1408~1418 (2003)
- Qiu L, "Differentially expressed proteins in the pancreas of diet-induced diabetic mice", Mol Cell Proteomics, 4, pp.1311~1318 (2005)
- Fraulob JC, "A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL", 6 mice fed a high fat diet, 2010, pp.46, 212~223
- Borst SE, "High-fat diet induces increased tissue expression of TNF-alpha", Life Sci, 77, pp.2156~2165 (2005)
- Mathur A, "Nonalcoholic fatty pancreas disease", HPB, 9, pp.312~318 (2007)
- Yan MX, "Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia", Biochem Biophys Res Commun, 347, pp.192~199 (2006)
- Zhang X, "Chronic high-fat diets induce oxide injuries and fibrogenesis of pancreatic cells in rats", Pancreas, 37, pp.e31~e38 (2008)
- Asaumi H, "Externally applied pressure activates pancreatic stellate cells through the generation of intracellular reactive oxygen species", Am J Physiol Gastrointest Liver Physiol, 293, pp.G972~G978 (2007)
- Omary MB, "The pancreatic stellate cell: a star on the rise in pancreatic diseases", J Clin Invest, 117, pp.50~59 (2007)
- Leung PS, "Role of oxidative stress in pancreatic inflammation", Antioxid Redox Signal, 11, pp.135~165 (2009)
- Shi H, "TLR4 links innate immunity and fatty acid-induced insulin resistance", J Clin Invest, 116, pp.3015~3025 (2006)
- Kim F, "Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity", Circ Res, 100, pp.1589~1596 (2007)
- Mews P, "Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis", Gut, 50, pp.535~541 (2002)
- Shek FW, "Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis", Am J Pathol, 160, pp.1787~1798 (2002)
- Masamune A, "Activated rat pancreatic stellate cells express intercellular adhesion molecule-1 (ICAM-1) in vitro", Pancreas, 25, pp.78~85 (2002)
- Czakó L, "Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats", Eur J Pharmacol, 572, pp.74~81 (2007)
- Gómez JA, "Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis", Am J Physiol Gastrointest Liver Physiol, 287, pp.G162~G169 (2004)
- Tasci I, "Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation", Pancreas, 35, pp.366~371 (2007)
- Chen F, "New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases", Clin Chem, 45, pp.7~17 (1999)
- Jokelainen K, "Nf-kappab activation is associated with free radical generation and endotoxemia and precedes pathological liver injury in experimental alcoholic liver disease", Cytokine, 16, pp.36~39 (2001)
- Parola M, "Oxidative stress-related molecules and liver fibrosis", J Hepatol, 35, pp.297~306 (2001)
- Hisada S, "Peroxisome proliferator-activated receptor gamma ligand prevents the development of chronic pancreatitis through modulating NF-kappaB-dependent proinflammatory cytokine production and pancreatic stellate cell activation", Rocz Akad Med Bialymst, 50, pp.142~147 (2005)
- Strauch ED, "Bile salts regulate intestinal epithelial cell migration by nuclear factor-kappa Binduced expression of transforming growth factor-beta", J Am Coll Surg, 197, pp.974~984 (2003)
- Shinozaki S, "IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-kappaB", TGF-beta1 pathway, 2010, pp.393, 61~65
- Ka SM, "Smad7 gene therapy ameliorates an autoimmune crescentic glomerulonephritis in mice", J Am Soc Nephrol, 18, pp.1777~1788 (2007)
- He J, "Protection of cerulein-induced pancreatic fibrosis by pancreas-specific expression of Smad7", Biochim Biophys Acta, 1792, pp.56~60 (2009)